Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure

Abstract

BackgroundInfants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. Early brain imaging in infancy has the potential to identify early brain developmental alterations that may help predict behavioral outcomes in these children. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants.Methods and MaterialsIn this prospective study, we recruited 23 infants with prenatal opioid exposure and 29 healthy opioid naïve infants. All subjects underwent brain resting-state functional MRI before 3 months postmenstrual age. Covariate Assisted Principal (CAP) regression was performed to identify brain networks within which functional connectivity was associated with opioid exposure after adjusting for sex and gestational age. Associations of these significant networks with maternal comorbidities were also evaluated. Additionally, graph network metrics were assessed in these CAP networks.ResultsThere were four CAP network components that were significantly different between the opioid exposed and healthy control infants. Two of these four networks were associated with maternal psychological factors. Intra-network graph metrics, namely average flow coefficient, clustering coefficient and transitivity were also significantly different in opioid exposed infants compared to healthy controls.ConclusionPrenatal opioid exposure is associated with alterations in global brain functional networks compared to non-opioid exposed infants, with intra-network alterations in graph network modeling. These network alterations were also associated with maternal comorbidity, especially mental health. Large-scale longitudinal studies can help in understanding the clinical implications of these early brain functional network alterations in infants with prenatal opioid exposure.

Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons

“…A significant challenge is distinguishing the neurobiological effects of opioid agonists from various other confounding factors, including tobacco, alcohol, nonmedical drugs, environmental influences, and additional medical risks ( Logan et al, 2013 ; Radhakrishnan et al, 2022a ; Radhakrishnan et al, 2022b ). The effects of opioids during pregnancy extend beyond nociceptive processes to include effects on gastrointestinal, endocrine, and autonomic functions as well as cognition, behavior, and reward circuitry for the mother and developing fetus, and subsequently the offspring ( Radhakrishnan et al, 2021 ; Radhakrishnan et al, 2022a ; Radhakrishnan et al, 2022b ; Radhakrishnan et al, 2022c ; Vishnubhotla et al, 2022 ; Wise et al, 2023 ).…”

Brain structural connectome in neonates with prenatal opioid exposure

“…Recent work showed alterations in amygdala and thalamocortical functional connectivity in infants with POE compared to controls (Radhakrishnan et al, 2020(Radhakrishnan et al, , 2022b). In addition, recent studies have also applied graph theoretical methods to understand further the brain functional connectivity alterations in POE and their associations with maternal comorbidities and clinical outcomes (Merhar et al, 2021;Radhakrishnan et al, 2022c). Due to differences in brain segmentation atlases, ROI selections and network connectivity analyses methods used in these prior rs-fMRI studies compared to our current DTI study, intermediary causal relationship of microstructural to functional network alterations is difficult to surmise.…”

Sex differences in neonatal outcomes following prenatal opioid exposure

“…Postnatal neuroimaging in opioid-exposed neonates demonstrated smaller deep gray matter structures (e.g., ventrolateral thalami, subthalamic nuclei) and smaller brainstem volumes adding to the evidence of alterations in these dopaminergic pathways ( 84 ). Resting-state functional imaging demonstrates global connectivity issues in neonates with prenatal opioid exposure, suggesting the involvement of various pathways and regions in aberrations related to opioid exposure ( 85 ). These small cohort studies have controlled for sex but were not designed to show sex differences, necessitating further investigation.…”